Long Term Outcomes with Selective Drug Eluting Stent Use in STElevation Myocardial Infarction in an Australian Urban Population

Aim: To evaluate the safety and effect on long-term outcomes of an approach that selectively uses drug-eluting stent (DES) only in ST elevation myocardial infarction (STEMI) that meet criteria for high risk of in-stent restenosis (ISR).Methods: Consecutive patients (n=1832) presenting with STEMI to a single large centre between April 2004 and January 2012 were managed according to an algorithm in which those with pre-specified criteria indicating they were at high risk for ISR received DES (46%, n=847), and otherwise received bare metal stents (BMS) (54%, n=985). High risk criteria included: vessel diameter £2.5mm (£3.0mm in diabetic patients); lesion length >18mm; previous ISR; saphenous vein graft lesions; ostial lesions; bifurcation lesions; left main coronary artery lesions; and multi-vessel disease. The two groups were compared for primary composite outcome of major adverse cardiac events (MACE) including death, repeat MI and TVR; and secondary outcomes of target lesion revascularisation (TLR) and stent thrombosis (ST).Results: Over a median period of 24 months there was no significant difference (DES vs BMS) in MACE (13.6% vs 18.1%, p=0.074), mortality (7.6% vs 10.5%, p=0.327) or definite stent thrombosis (2.6% vs 1.6%, p=0.094). Patients who received DES had a lower rate of clinically driven TLR (1.6% vs 3.9%, p=0.032).Conclusion: An approach of selectively using DES in STEMI patients at high risk of ISR provides satisfactory long-term outcomes while limiting the number of patients exposed to DES costs

Singlet molecular oxygen regulates vascular tone and blood pressure in inflammation

Singlet molecular oxygen (O-1(2)) has well-established roles in photosynthetic plants, bacteria and fungi(1-3), but not in mammals. Chemically generated O-1(2) oxidizes the amino acid tryptophan to precursors of a key metabolite called N-formylkynurenine(4), whereas enzymatic oxidation of tryptophan to N-formylkynurenine is catalysed by a family of dioxygenases, including indoleamine 2,3-dioxygenase 1(5). Under inflammatory conditions, this haem-containing enzyme is expressed in arterial endothelial cells, where it contributes to the regulation of blood pressure(6). However, whether indoleamine 2,3-dioxygenase 1 forms O-1(2) and whether this contributes to blood pressure control have remained unknown. Here we show that arterial indoleamine 2,3-dioxygenase 1 regulates blood pressure via formation of O-1(2). We observed that in the presence of hydrogen peroxide, the enzyme generates O-1(2) and that this is associated with the stereoselective oxidation of L-tryptophan to a tricyclic hydroperoxide via a previously unrecognized oxidative activation of the dioxygenase activity. The tryptophan-derived hydroperoxide acts in vivo as a signalling molecule, inducing arterial relaxation and decreasing blood pressure; this activity is dependent on Cys42 of protein kinase G1 alpha. Our findings demonstrate a pathophysiological role for O-1(2) in mammals through formation of an amino acid-derived hydroperoxide that regulates vascular tone and blood pressure under inflammatory conditions